Micro- and Nanotechnologies-Based Product Development

Description

This book provides comprehensive information of the nanotechnology-based pharmaceutical product development including a diverse range of arenas such as liposomes, nanoparticles, fullerenes, hydrogels, thermally responsive externally activated theranostics (TREAT), hydrogels, microspheres, micro- and nanoemulsions and carbon nanomaterials. It covers the micro- and nanotechnological aspects for pharmaceutical product development with the product development point of view and also covers the industrial aspects, novel technologies, stability studies, validation, safety and toxicity profiles, regulatory perspectives, scale-up technologies and fundamental concept in the development of products. Salient Features: Covers micro- and nanotechnology approaches with current trends with safety and efficacy in product development. Presents an overview of the recent progress of stability testing, reverse engineering, validation and regulatory perspectives as per regulatory requirements. Provides a comprehensive overview of the latest research related to micro- and nanotechnologies including designing, optimisation, validation and scale-up of micro- and nanotechnologies. Is edited by two well-known researchers by contribution of vivid chapters from renowned scientists across the globe in the field of pharmaceutical sciences. Dr. Neelesh Kumar Mehra is working as an Assistant Professor of Pharmaceutics & Biopharmaceutics at the Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, India. He received ‘TEAM AWARD’ for successful commercialisation of an ophthalmic suspension product. He has authored more than 60 peer-reviewed publications in highly reputed international journals and more than 10 book chapter contributions. He has filed patents on manufacturing process and composition to improved therapeutic efficacy for topical delivery. He guided PhD and MS students for their dissertations/research projects. He has received numerous outstanding awards including Young Scientist Award and Team Award for his research output. He recently published one edited book, ‘Dendrimers in Nanomedicine: Concept, Theory and Regulatory Perspectives’, in CRC Press. Currently, he is editing books on nano drug delivery-based products with Elsevier Pvt Ltd. He has rich research and teaching experience in the formulation and development of complex, innovative ophthalmic and injectable biopharmaceutical products including micro- and nanotechnologies for regulated market. Dr. Arvind Gulbake is working as an Assistant Professor at the Faculty of Pharmacy, School of Pharmaceutical & Population Health Informatics, at DIT University, Dehradun, India. He has authored more than 40 peer-reviewed publications in highly reputed international journals, four book chapters and a patent contribution. He has received outstanding awards including Young Scientist Award and BRG Travel Award for his research. He is an assistant editor for IJAP. He guided PhD and MS students for their dissertations/research projects. He has successfully completed extramural project funded by SERB, New Delhi, Government of India. He has more than 12 years of research and teaching experience in the formulation and development of nanopharmaceuticals. Cover Half Title Title Page Copyright Page Table of Contents Preface Editors List of Contributors Section A Introduction Chapter 1 Micro- and Nanotechnology Approaches: Concepts and Applications 1.1 Introduction 1.1.1 Structure and Classification 1.1.2 Synthesis 1.2 Characterisation Techniques 1.3 Properties of Particles 1.4 Pharmacokinetics, Toxicity and Biodistribution 1.5 Applications 1.5.1 Bioavailability Improvements 1.5.2 Theranostic Agent 1.5.3 Multidrug Resistance 1.6 Stability of Active Pharmaceutical Ingredients (API) 1.7 Marketed Approval of NP Drug Delivery and Regulatory Status 1.7.1 Nanomedicines: Current Status and Future Perspectives in the Aspects of Drug Delivery and Pharmacokinetics 1.8 Future of Nanomedicines and Drug Delivery Systems 1.9 Conclusion and Future Perspectives Acknowledgement References Chapter 2 Formulation by Design (FbD): An Emerging Approach to Design Vesicular Nanocarriers Abbreviations 2.1 Introduction 2.2 FbD Terminology 2.3 The Methodology of FbD Optimisation 2.3.1 Step I − Defining Formulation Objectives 2.3.2 Step II − Selection of Significant Factors and Response Variables 2.3.3 Step III − Formulation Development as per ED 2.3.4 Step IV − Modelisation and Search for Optimum Formulation 2.3.5 Step V − Validation Studies and Scale-Up 2.4 Design of Experiments 2.4.1 Experimental Designs 2.4.2 Selection of ED 2.4.2.1 Comparative Objective 2.4.2.2 Screening Objective 2.4.2.3 Response Surface Method Objective 2.4.3 Various EDs for the Optimisation of Nanovesicles 2.4.3.1 Factorial Design 2.4.3.2 Central Composite Design (CCD) 2.4.3.3 Box−Behnken Design (BBD) 2.4.3.4 Simple Mixture Design (SMD) 2.4.3.5 Optimal Design 2.4.3.6 Fractional Factorial Design (FFD) 2.4.3.7 Taguchi Design (TgD) 2.4.3.8 Plackett−Burman Design (PBD) 2.5 Application of QbD 2.5.1 Liposomes 2.5.2 Niosomes 2.5.3 Transferosomes 2.5.4 Pharmacosomes and Ufasomes 2.5.5 Aquasomes and Polymeric Micelles 2.6 Conclusion and Prospects Acknowledgement Conflict of Interest References Chapter 3 Thermally Responsive Externally Activated Theranostics (TREAT) for On-Demand Multifunctional Drug Delivery Systems 3.1 Introduction 3.1.1 Concept behind TREAT 3.2 Thermally Responsive Polymers and Nanocarriers 3.3 Diagnostic Approach 3.4 Optical Imaging 3.5 Magnetic Resonance Imaging (MRI) 3.6 Ultrasound (US) 3.7 Computed Tomography (CT) 3.8 Single-Photon Emission Computed Tomography and Positron Emission Tomography 3.9 Conclusions and Future Directions Conflict of Interest References Chapter 4 C[sub(60)]-Fullerenes as an Emerging Cargo Carrier for the Delivery of Anti-Neoplastic Agents: Promises and Challenges 4.1 Introduction 4.2 Synthetic Methods of C[sub(60)]Fs 4.2.1 Arc Vaporisation Technique 4.2.2 Laser Ablation 4.2.3 Hydrocarbon Combustion 4.2.4 Other Methods 4.5 Functionalisation of C[sub(60)]Fs 4.5.1 Nucleophilic Addition Reactions 4.5.1.1 Bingel Reactions 4.5.1.2 Addition of Ylides 4.5.2 Cycloaddition Reactions 4.5.3 Miscellaneous Functionalisations 4.6 Medical Applications of C[sub(60)]Fs 4.6.1 Antioxidant and Neuroprotective Agent 4.6.2 Antiviral Agent 4.6.3 Photodynamic Therapy 4.6.4 Anti-Inflammatory Agent 4.6.5 Antitumour Agent 4.7 C[sub(60)]Fs as Drug Delivery Carriers to Neoplastic Cells 4.8 Toxicity Profile and the Challenges of C[sub(60)]Fs 4.9 Conclusions Conflict of Interest References Section B Bioactive Delivery Systems Chapter 5 Pharmaceutical and Biomedical Applications of Multifunctional Quantum Dots 5.1 Introduction 5.2 History of QDs 5.3 Types of QDs 5.4 Synthesis of QDs 5.4.1 Organic-Phase Method/Organometallic Chemistry Method 5.4.2 Water-Phase Method/Aqueous Solution Method 5.4.3 Hydrothermal and Microwave-Assisted Irradiation Methods 5.4.4 Laser Ablation Techniques for QDs 5.4.5 Molecular Beam Epitaxy (MBE) and Nanopatterning for QDs 5.5 Properties of QDs 5.6 Biomedical Applications of QDs 5.6.1 In Vivo Cell Imaging 5.6.1.1 Synaptic Neurotransmission 5.6.1.2 Single Protein Tracking 5.6.1.3 Cell Tracking and Migration 5.6.2 In Vitro/Ex Vivo Cell Imaging 5.6.3 Tissue Imaging 5.6.4 Diagnostic Tool for Detection of Diseases 5.6.5 Development of Diagnostic Test Systems 5.6.6 Biosensors/Biomarkers for Detection of Mutation, Multiplexed Target and miRNA Detection 5.6.7 Drug Delivery/Carrier for Treatment 5.6.7.1 Ocular Diseases 5.6.7.2 Cardiovascular Diseases 5.6.7.3 Neurological Disorders 5.6.7.4 Hepatic Diseases 5.6.7.5 Antibiotic-Resistant Infection 5.6.7.6 Tumours 5.6.7.7 Renal Diseases 5.6.7.8 Others 5.6.8 Cell Labelling 5.7 Conclusion References Chapter 6 PLGA-Based Micro- and Nano-particles: From Lab to Market Abbreviations 6.1 Introduction 6.2 Physicochemical Properties of PLGA 6.2.1 Molecular Weight 6.2.2 Solubility 6.2.3 Polymer Erosion 6.2.4 PLA to PGA Content 6.2.5 Glass Transition Temperature (Tg) 6.3 Advantages and Limitations of PLGA 6.4 PLGA Application 6.4.1 Controlled and Sustained Drug Delivery 6.4.2 Drug Stabilisation 6.4.3 Targeted Drug Delivery 6.4.4 PLGA-Based Carrier System for Remotely Stimulated Cancer Therapy 6.5 PLGA-Based Commercially Available Products 6.6 Challenges for PLGA-Based Drug Delivery Systems – Clinical and Commercial Success 6.6.1 Scale-Up and Large-Scale Production 6.6.2 Biocompatibility and Safety Challenges 6.6.3 Intellectual Property (IP) 6.6.4 Regulatory Requirements 6.7 Conclusion and Future Perspectives for PLGA as Carrier System References Chapter 7 Targeted Lipid-Based Nanoparticles for Nucleic Acid Delivery in Cancer Therapy Abbreviations 7.1 Introduction 7.2 Lipid Nanosystems for Nucleic Acid Delivery in Cancer 7.2.1 Lipoplexes (Liposome + Nucleic Acid) 7.2.2 Solid-Lipid Nanoparticles (SLNs) 7.2.3 Nanostructured Lipid Carriers (NLCs) 7.2.4 Stable Nucleic Acid-Lipid Particles (SNALPs) 7.2.5 High-Density Lipoproteins (HDL) 7.2.6 Lipidoids 7.3 Clinical Trials Involving Lipid Nanosystems for Nucleic Acid Delivery in Cancer 7.4 Conclusion and Future Prospects References Chapter 8 Formulation Strategies for Improved Ophthalmic Delivery of Hydrophilic Drugs Abbreviations 8.1 Introduction 8.1.1 Barriers for Ocular Delivery of Hydrophilic Therapeutics 8.2 Approaches to Improve Ocular Permeability of Hydrophilic Therapeutics 8.2.1 Development of Prodrugs 8.2.2 Use of Permeation Enhancers 8.2.3 Use of Chemical Chaperones (Protein Aggregation Inhibitors) 8.2.4 By Incorporating into Colloidal Nanoparticles (NPs) 8.2.4.1 Emulsions 8.2.4.2 Polymeric Nanoparticles (NPs) and Microparticles (MPs) 8.2.4.3 Micelles 8.2.4.4 Reverse Micelles (RMs) 8.2.4.5 Liposomes 8.2.4.6 Niosomes 8.2.4.7 Discomes/Cubosomes 8.2.4.8 Spanlastics 8.2.4.9 Lipid NPs 8.2.4.10 Dendrimers 8.2.4.11 Nanocrystals 8.3 Chief Challenges for Nanoparticulate Delivery of Hydrophilic Therapeutics 8.3.1 Poor Drug Loading Efficiency 8.3.2 Poor Ocular Residential Time 8.4 Approaches to Improve Loading of Hydrophilic Therapeutics in Colloidal NPs 8.4.1 Development of Carrier–Drug Conjugate Nanoparticles (CDC-NPs) 8.4.1.1 Ester Bonds 8.4.1.2 Amide Bonds 8.4.1.3 Hydrazone Bonds 8.4.1.4 Disulphide Bonds 8.4.1.5 Other Bonds 8.4.1.6 Self-Assembled NPs (Carrier-free System) 8.4.1.7 Micelles 8.4.1.8 Emulsions 8.4.1.9 Polymeric NPs 8.4.1.10 Lipid NPs 8.4.1.11 Liposomes 8.4.2 Development of Nanoplexes 8.4.2.1 Lipoplexes 8.4.2.2 Polyplexes 8.4.2.3 Micelleplexes 8.5 Approaches to Improve Ocular Residence Time of Colloidal Carriers 8.5.1 Development of Mucoadhesive Colloidal NPs 8.5.2 Development of Colloidal NP-laden Composite Systems 8.5.2.1 NP-laden In Situ Gel 8.5.2.2 NP-laden Hydrogels 8.5.2.3 NP-laden Contact Lenses 8.5.2.4 NP-Laden Ocular Inserts 8.5.3 Development of Nanowafers 8.6 Advanced/Future Treatment Approaches 8.6.1 Nucleic Acid-Based Therapy over Small Molecule Drugs 8.6.2 Optogenetics 8.6.3 Stem Cells and Cell Transplantation Techniques 8.6.4 Encapsulated Cell Technology (ECT) 8.6.5 Noble Metal NPs with Multiple Functions 8.6.6 Targeted NPs 8.6.7 Theranostic NPs 8.6.8 Microneedle-laden Collagen Cryogel Plugs 8.6.9 Use of Physical Methods in Combination with Chemical Approaches 8.7 Regulatory and Future Perspectives 8.8 Conclusions Acknowledgements References Chapter 9 Metal Nanoparticles as a Surrogate Carrier in Drug Delivery and Diagnostics 9.1 Introduction 9.1.1 Advantages/Benefits of Metal Nanoparticles 9.1.2 Limitations of Metal Nanoparticles 9.2 Types of Metal Nanoparticles 9.2.1 Gold Nanoparticles (AuNPs) 9.2.1.1 Synthesis of Gold Nanoparticles (AuNPs) 9.2.1.2 Applications of Gold Nanoparticles (AuNPs) 9.2.2 Silver Nanoparticles (AgNPs) 9.2.2.1 Synthesis of Silver Nanoparticles (AgNPs) 9.2.2.2 Applications of Silver Nanoparticles (AgNPs) 9.2.3 Zinc Oxide Nanoparticles (ZnO NPs) 9.2.3.1 Synthesis of Zinc Oxide Nanoparticles (ZnO NPs) 9.2.3.2 Applications of Zinc Oxide Nanoparticles (ZnO NPs) 9.2.4 Iron Oxide Nanoparticles (FeO NPs) 9.2.4.1 Synthesis of Iron Oxide Nanoparticles (FeNPs) 9.2.4.2 Biomedical Applications of Iron Oxide 9.2.5 Zirconium Nanoparticles (ZrNPs) 9.2.5.1 Synthesis of Zirconia Nanoparticles 9.2.5.2 Applications of Zirconia Nanoparticles 9.3 Characterisation Techniques of Nanoparticles 9.3.1 Energy-Dispersive X-Ray Spectroscopy (EDX) 9.3.2 Fourier Transform Infrared Spectroscopy (FTIR) 9.3.3 Scanning Electron Microscopy (SEM) 9.3.4 Transmission Electron Microscope (TEM) 9.3.5 Particle Size Analyser 9.3.6 X-Ray Diffraction (XRD) 9.3.7 Atomic Force Microscopy (AFM) 9.3.8 Ultraviolet (UV) Spectroscopy 9.3.9 Dynamic Light Scattering (DLS) 9.3.10 Zeta Potential 9.3.11 Nanoparticle Tracking Analysis (NTA) 9.4 Applications of Metallic Nanoparticles 9.4.1 Metallic Nanoparticles in Cancer Therapy 9.4.2 Nanoparticles for Delivering Peptides and Proteins 9.4.3 Nanoparticles in Drug Discovery 9.4.4 Ocular Drug Delivery 9.4.5 Nanoparticles in Molecular Diagnostics/Molecular Imaging 9.4.6 Nanoparticles as Biosensors and Biolabels 9.4.7 Carriers for Nasal Vaccine/Drug Delivery 9.4.8 Nutraceutical Delivery 9.5 Green Technology 9.5.1 Principle 9.5.2 Mechanism 9.5.3 Advantages of Green Synthesis of Nanoparticles 9.5.4 Synthesis of Metallic Nanoparticles from Green Synthesis 9.6 Conclusion References Chapter 10 Resealed Erythrocytes: A Biological Carrier for Drug Delivery Abbreviations 10.1 Introduction 10.2 Red Blood Cells 10.3 Erythrocytes as Cellular Carriers 10.4 Erythrocytes as Drug Delivery System 10.5 Benefit of Erythrocytes as Drug Carriers 10.6 Drawbacks of Erythrocytes as Drug Carriers 10.7 Provisions for Drug Encapsulation into Erythrocytes 10.7.1 Isolation of Erythrocytes 10.7.2 Method of Drug Loading 10.8 Characterisation of Drug-Loaded Erythrocytes 10.9 Applications of Resealed Erythrocytes 10.9.1 Erythrocytes as Drug Delivery Systems 10.9.2 Drug Targeting 10.9.3 Enzyme and Hormones Deficiency/Replacement Therapy 10.9.4 Treatment of Solid Tumours 10.9.5 Treatment of Parasitic Diseases 10.9.6 Treatment of Heavy Metal and Toxic Agent Poisoning 10.9.7 Lead Poisoning Treatment 10.9.8 Antibody Attachment to Erythrocyte Membrane 10.9.9 Delivery of Antiviral Agents 10.9.10 Improvement in Atomic Number 8 Delivery to Tissues 10.9.11 Microinjection of Macromolecules 10.10 Safety Concern with Carrier Erythrocytes 10.11 Conclusion Acknowledgement References Chapter 11 Nanostructured Hydrogel-Based Biosensor Platform Abbreviations 11.1 Introduction 11.2 Hydrogels in Biosensor Platform 11.2.1 Nanoparticle-Incorporated Hydrogel Biosensor 11.2.1.1 Metal Nanoparticles 11.2.1.2 Carbon Nanostructure 11.2.2 Conducting Polymer (CP)-Based Hydrogel Biosensor 11.2.3 Biomolecule-Incorporated Hydrogel Biosensor 11.3 Biomedical Application of Hydrogel-Based Sensors 11.4 Conclusion Acknowledgement References Chapter 12 Multifunctional Carbon Nanotubes in Drug Delivery 12.1 Introduction 12.1.1 History 12.1.2 Structure of CNTs 12.1.3 Types of CNTs 12.1.4 Properties of CNTs 12.1.5 Synthesis Methods of CNTs 12.1.6 Recent Trends of CNT's Synthesis 12.1.6.1 Vapour-Phase Growth 12.1.6.2 Nebulised Spray Pyrolysis Method 12.1.6.3 High-Pressure Carbon Monoxide (HiPco) 12.2 Purification and Functionalisation Techniques of CNTs/Dispersion of CNTs 12.2.1 Purification 12.2.1.1 Oxidation 12.2.1.2 Acid Purification 12.2.1.3 Annealing 12.2.2 Functionalisation Techniques of CNTs 12.2.2.1 Covalent Functionalisation 12.2.2.2 Non-Covalent Functionalisation of CNTs 12.2.3 Characterisation of CNTs 12.3 Cell Penetration and Mechanism of Multifunctional CNTs 12.4 Application of Multifunctional Carbon Nanotubes in Drug Delivery 12.5 Toxicological Perspectives of CNTs 12.6 Recent Patents Related to CNTs as a Drug Delivery System 12.7 Conclusions and Future Perspectives Conflict of Interest Acknowledgement References Section C Product Development, Toxicity and Scale-Up Chapter 13 Liposomal-Based Pharmaceutical Formulations – Current Landscape, Limitations and Technologies for Industrial Scale-Up 13.1 Introduction 13.2 Industrial-Scale Production of Liposomes 13.3 Liposomal Techniques for Delivery of Drugs 13.3.1 Stealth Liposome Technology 13.3.2 Non-PEGylated Liposome Technology 13.3.3 DepoFoam™ Liposome Technology 13.3.4 Lysolipid Thermally Sensitive Liposome (LTSL) Technology 13.4 Biological Defies Faced by Liposomes 13.4.1 The Reticuloendothelial System (RES) and Liposome Clearance 13.4.2 Opsonins and Vesicle Destabilisation 13.4.3 The Enhanced Permeability and Retention (EPR) Effect 13.4.4 The Accelerated Blood Clearance (ABC) Phenomenon 13.4.5 Complement Activation-Related Pseudoallergy (CARPA) 13.5 Clinically Approved Liposomal-Based Drugs 13.6 Defies for Continuous Manufacturing of Liposomes 13.6.1 Formulation Refinement 13.6.2 Materials Employed in Production 13.6.3 Assuring Sterility 13.7 Regulatory Aspects for Approval of New Systems of Drug Delivery 13.8 Conclusion and Future Perspectives References Chapter 14 Impact and Role of Stability Studies in Parenteral Product Development Abbreviations 14.1 Introduction 14.2 Importance of Stability Studies in Parenteral Products 14.3 Formulation Development and Stability Studies of a Parenteral/Sterile Product 14.4 Stability Testing Methodologies of Sterile Products 14.4.1 Real-time Stability Study 14.4.2 Accelerated Stability Studies 14.4.3 Retained Sample Stability Studies 14.4.4 Cyclic Temperature Stress Studies 14.5 Regulatory Guidelines for Stability Studies of Parenterals [1G] 14.5.1 ICH and WHO Stability Study Guidelines 14.5.2 CPMP Stability Study Guidelines 14.6 Protocol for Stability Study of Parenteral 14.6.1 Testing Sample 14.6.2 Testing of Containers and Closure System of Product 14.6.3 Frequency of Testing and Sampling Plan 14.6.4 Storage Conditions for Testing Samples 14.6.5 Testing Parameters and Acceptance of Stability Study Data 14.6.6 Recording the Stability Study Data 14.6.7 Estimation of Shelf Life and Expiration Date 14.7 Current Trends in Parenteral Formulation and Stability Studies 14.8 Conclusion References Chapter 15 Reverse Engineering in Pharmaceutical Product Development Abbreviations 15.1 Introduction 15.2 Pharmaceutical Reverse Engineering in Formulation Development 15.2.1 Why to Reverse the Pharmaceutical Product Development Process 15.2.2 How to Reverse the Pharmaceutical Product Development Process 15.2.3 Common Analytical Methods for Reverse Pharmaceutical Engineering 15.3 Reverse Pharmaceutical Engineering for Generic Product Development 15.3.1 Reverse Engineering of a Tablet 15.3.2 Reverse Engineering of a Capsule 15.3.3 Reverse Engineering of Lipid Emulsion 15.3.4 Reverse Engineering of Ocular Product 15.3.5 Reverse Engineering of a Depot Microsphere Formulation 15.4 Reverse Pharmaceutical Engineering of Herbal Product 15.5 Reverse Engineering for Stability Testing of Newer Drugs 15.6 Conclusion and Future Prospects Acknowledgement Conflict of Interest References Chapter 16 Role of Polymers in Formulation Design and Drug Delivery 16.1 Introduction 16.2 Classification of Polymers 16.2.1 Polymers Based on Origin 16.2.2 Based on Degradation 16.3 Polymers in Pharmaceutical Drug Delivery System 16.4 Responsive Polymer for Drug Delivery 16.4.1 Mucoadhesive 16.4.2 Thiolated Polymers 16.4.3 pH-Sensitive Polymers 16.4.4 Temperature-Sensitive 16.4.5 Temperature-Responsive Polymers 16.4.6 Ionic-Sensitive Polymers 16.4.7 Biodegradable 16.4.8 Viscosity Enhancer 16.4.9 Highly Water-Soluble Polymer 16.5 Role of Polymer in Drug Delivery System 16.5.1 Modified Drug-Release Dosage Forms 16.5.2 Extended-Release Dosage Forms 16.5.3 Gastro-retentive Dosage Forms 16.6 Types of Polymers in Pharmaceutical Drug Delivery 16.6.1 Polymers in Colon-Targeted Drug Delivery 16.6.2 Polymers in the Mucoadhesive Drug Delivery System 16.6.3 Polymers for Sustained Release 16.6.4 Polymers in Tissue Engineering 16.7 In Situ Drug Delivery System 16.8 Polymer–Drug Conjugate Acknowledgement References Chapter 17 Drug Delivery Systems for Targeting Blood Brain Barrier: Examples of nanomedicines for the treatment of neurodegenerative diseases Abbreviations 17.1 Introduction 17.2 The Blood–Brain Barrier 17.3 Pharmacotherapy 17.4 Nanoparticles for Targeting the CNS 17.4.1 Mesoporous Silica Nanoparticles 17.4.2 Gold Nanoparticles 17.4.3 Polymeric Nanoparticles 17.4.4 Liposomes 17.4.5 Solid Lipid Nanoparticles 17.4.6 Nanostructured Lipid Carriers 17.4.7 Quantum Dots 17.4.8 Fullerenes 17.4.9 Carbon Nanotubes 17.4.10 Dendrimers 17.4.11 Nanogels 17.4.12 Micelles 17.5 Examples of Nanomedicines for Alzheimer's Disease 17.5.1 Modulation of Aβ Production 17.5.2 Inhibition of Aβ Production 17.5.3 Improvement of Aβ Clearance 17.6 Examples of Nanomedicines for Parkinson's Disease 17.6.1 Dopamine Replacement 17.6.2 Targeting α-Synuclein Accumulation 17.6.2 Targeting Inflammation 17.6.3 Targeting Antioxidative Stress 17.6.4 Neurotrophic Factor Supplementation 17.7 Sterilisation of Nanomaterials 17.8 Conclusions Acknowledgements References Chapter 18 Validation, Scale-Up and Technology Transfer in Product Development Abbreviations 18.1 Introduction 18.2 Validation 18.2.1 Types of Validation 18.2.1.1 Process Validation 18.2.1.2 Process Validation and Drug Quality 18.2.2 Computer System Validation (Process Controller) 18.2.2.1 Computer System Validation Process 18.2.3 Cleaning Validation 18.2.3.1 General Requirement 18.2.3.2 Evaluation of Cleaning Validation 18.2.4 Analytical Method Validation 18.3 Scale-Up and Technology Transfer in Pharmaceutical Product Development 18.3.1 Process Transfer: An Overall Framework 18.3.2 Goal of Technology Transfer 18.3.3 Steps in Technology Transfer 18.3.3.1 Quality by Design in Scale-Up 18.4 Importance of Technology Transfer 18.5 Conclusion Acknowledgement References Chapter 19 Nanotoxicology: Safety, Toxicity and Regulatory Considerations Abbreviations 19.1 Introduction 19.2 Nanomedicine 19.3 Nanotoxicology 19.3.1 Mechanisms of NP Toxicity 19.3.2 ROS and Oxidative Stress 19.3.3 Genotoxicity 19.3.4 Inflammation 19.3.5 Fibrosis 19.3.6 Cancer 19.3.7 Crossing Biological Barriers 19.4 Target Organ Toxicity 19.4.1 Kidney Toxicity 19.4.2 Cardiotoxicity 19.4.3 Brain Toxicity 19.4.4 Lung Toxicity 19.4.5 Spleen Toxicity 19.4.6 Liver Toxicity 19.4.7 Inhalational Toxicity 19.4.8 RES Toxicity 19.5 Biodistribution and Biodegradation 19.5.1 Biodistribution 19.5.2 Biodegradation 19.6 Factors Affecting Nanoparticle Toxicity 19.6.1 Particle Size and Surface Area 19.6.2 Particle Shape 19.6.3 Surface Characteristics 19.6.4 Composition and Crystalline Structure 19.6.5 Agglomeration and Solvent/Medium 19.6.6 Route of Exposure 19.7 Toxicity Studies 19.7.1 In Vitro Nanotoxicity Assessment Methods 19.7.2 In Vivo Nanotoxicity Assessment Methods 19.8 Role of Omics and 3D Models in Nanotoxicology 19.9 Regulatory Status 19.10 Conclusion and Future Perspectives Conflict of Interest References Index